Adverse anthropometric risk profile in biochemically controlled acromegalic patients: comparison with an age- and gender-matched primary care population

GH and IGF-1 play an important role in the regulation of metabolism and body composition. In patients with uncontrolled acromegaly, cardiovascular morbidity and mortality are increased but are supposed to be normalised after biochemical control is achieved. We aimed at comparing body composition and the cardiovascular risk profile in patients with controlled acromegaly and controls. A cross-sectional study. We evaluated anthropometric parameters (height, weight, body mass index (BMI), waist and hip circumference, waist to height ratio) and, additionally, cardiovascular risk biomarkers (fasting plasma glucose, HbA1c, triglycerides, total cholesterol, HDL, LDL, and lipoprotein (a), in 81 acromegalic patients (58% cured) compared to 320 age- and gender-matched controls (ratio 1:4), sampled from the primary care patient cohort DETECT. The whole group of 81 acromegalic patients presented with significantly higher anthropometric parameters, such as weight, BMI, waist and hip circumference, but with more favourable cardiovascular risk biomarkers, such as fasting plasma glucose, total cholesterol, triglycerides and HDL levels, in comparison to their respective controls. Biochemically controlled acromegalic patients again showed significantly higher measurements of obesity, mainly visceral adiposity, than age- and gender-matched control patients (BMI 29.5 ± 5.9 vs. 27.3 ± 5.8 kg/m2; P = 0.020; waist circumference 100.9 ± 16.8 vs. 94.8 ± 15.5 cm; P = 0.031; hip circumference 110.7 ± 9.9 vs. 105.0 ± 11.7 cm; P = 0.001). No differences in the classical cardiovascular biomarkers were detected except for fasting plasma glucose and triglycerides. This effect could not be attributed to a higher prevalence of type 2 diabetes mellitus in the acromegalic patient group, since stratified analyses between the subgroup of patients with acromegaly and controls, both with type 2 diabetes mellitus, revealed that there were no significant differences in the anthropometric measurements. Biochemically cured acromegalic patients pertain an adverse anthropometric risk profile, mainly because of elevated adiposity measurements, such as BMI, waist and hip circumference, compared to an age- and gender-matched primary care population

Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to resistance; and strengthen the case for a role in survival of systems involved in manganese and iron homeostasis

Acromegaly

Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated at 1:140,000–250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected). Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH) responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Muscle Hypertrophy in Prepubescent Tennis Players: A Segmentation MRI Study

PURPOSE: To asses if tennis at prepubertal age elicits the hypertrophy of dominant arm muscles. METHODS: The volume of the muscles of both arms was determined using magnetic resonance imaging (MRI) in 7 male prepubertal tennis players (TP) and 7 non-active control subjects (CG) (mean age 11.0 ± 0.8 years, Tanner 1-2). RESULTS: TP had 13% greater total muscle volume in the dominant than in the contralateral arm. The magnitude of inter-arm asymmetry was greater in TP than in CG (13 vs 3%, P<0.001). The dominant arm of TP was 16% greater than the dominant arm of CG (P<0.01), whilst non-dominant arms had similar total muscle volumes in both groups (P = 0.25), after accounting for height as covariate. In TP, dominant deltoid (11%), forearm supinator (55%) and forearm flexors (21%) and extensors (25%) were hypertrophied compared to the contralateral arm (P<0.05). In CG, the dominant supinator muscle was bigger than its contralateral homonimous (63%, P<0.05). CONCLUSIONS: Tennis at prepubertal age is associated with marked hypertrophy of the dominant arm, leading to a marked level of asymmetry (+13%), much greater than observed in non-active controls (+3%). Therefore, tennis particpation at prepubertal age is associated with increased muscle volumes in dominant compared to the non-dominant arm, likely due to selectively hypertrophy of the loaded muscles

Piccolo genotype modulates neural correlates of emotion processing but not executive functioning

Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene—involved in monoaminergic neurotransmission—as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging (fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD

Gene Expression Profiling of Human Decidual Macrophages: Evidence for Immunosuppressive Phenotype

Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known. Methodology/Principal Findings: Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications. Conclusions/Significance: The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.Original Publication:Charlotte Gustafsson (Lidström), Jenny Mjösberg, Andreas Matussek, Robert Geffers, Leif Matthiesen, Göran Berg, Surendra Sharma, Jan Buer and Jan Ernerudh, Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype, 2008, PLoS ONE, (3), 4, e2078.http://dx.doi.org/10.1371/journal.pone.0002078Copyright: Public Library of Science (PLoS)http://www.plos.org